Detecting tau in serum of transgenic animal models after tau immunotherapy treatment
| Autor: | Giuseppe Terracina, Peter Davies, Stefanie K. Forest, Joel B. Schachter, Xiaohai Wang, Cristina d'Abramo, Christopher M. Acker |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Aging Tau pathology medicine.medical_treatment Transgene Mice Transgenic tau Proteins Antibodies Article 03 medical and health sciences 0302 clinical medicine Predictive Value of Tests mental disorders medicine Animals Humans Potential mechanism biology business.industry General Neuroscience Passive Immunotherapy Immunization Passive Immunotherapy Hydrogen-Ion Concentration Peripheral Disease Models Animal 030104 developmental biology Tauopathies Immunology biology.protein Neurology (clinical) Geriatrics and Gerontology Antibody business 030217 neurology & neurosurgery Biomarkers Developmental Biology |
| Zdroj: | Neurobiology of aging. 37 |
| ISSN: | 1558-1497 |
| Popis: | In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely. |
| Databáze: | OpenAIRE |
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